Low density lipoprotein (LDLs) plays a major role in cholesterol transport in blood and are risk factors for arteriosclerotic diseases. It is known that small, dense lipoprotein (hereinafter, referred to as “small, dense LDL”), which is particularly small in particle size among LDL and higher in specific gravity compared with standard LDL, have arteriosclerosis-inducing ability at a level several times higher than that of normal LDL.
Familial combined hyperlipidemia (hereinafter, referred to as “FCHL”) is based on type IIb phenotype under WHO classification of hyperlipidemia by type. FCHL shifts to type IIa or IV because of factors such as diet. Familial hyperlipidemia does not present any specific type, so that it is defined as hereditary hyperlipidemia presenting various phenotypes including Ia, IIb, and IV. FCHL is a type of primary hyperlipidemia that tends to cause arteriosclerotic diseases. It is said that the frequency of FCHL is extremely high, impacting about one out of 100 persons and 30% or more of FCHL cases causes coronary artery diseases.
The presence of small, dense LDL in blood samples of FCHL patients has been suggested by analysis using electrophoresis (see Journal of Lipid Research 2002; 43: 598-603; Circulation 2004; 109: 2980-2985; and Research Report on Specified Diseases, Primary Hyperlipidemia, 2000, Research Division of the Ministry of Health, Labour and Welfare (2000: 37-41)). The presence of small, dense LDL is demonstrated by the fact that analysis of the electrophoretic image of a blood sample using a densitometer results in 25.5 nm or less as an LDL main peak. This suggests the quality of LDL that is microparticulated. Furthermore, in FCHL, very low density lipoprotein (VLDLs) is synthesized excessively. Hence, it has been suggested that apoprotein B is thus present excessively relative to LDL cholesterol and then the ratio of apoprotein B to LDL cholesterol increases (see Research Report on Specified Diseases, Primary hyperlipidemia, 2000, Research Division of the Ministry of Health, Labour and Welfare (2000: 37-41)). In small, dense LDL, while the content (percentage) of cholesterol in LDL particles decreases, one molecule of apoprotein B is always present in one molecule of an LDL particle. Thus, it can be said that an increased ratio of apoprotein B to LDL cholesterol indirectly indicates the presence of small, dense LDL.
However, when LDL of normal sizes other than small, dense LDs increases together with small, dense LDL, the presence of small, dense LDL cannot be precisely and specifically detected with the above method, which involves finding the quality of LDL. This may result in misdiagnosis concerning whether or not a subject disease is familial combined hyperlipidemia. Moreover, when only the measured value of apoprotein B is used, evaluation is made with the inclusion of hyper-remnant blood diseases, resulting in low detection accuracy.